Evidence of Antimicrobial Resistance in Bats and Its Planetary Health Impact for Surveillance of Zoonotic Spillover Events: A Scoping Review.

As a result of the COVID-19 pandemic, as well as other outbreaks, such as SARS and Ebola, bats are recognized as a critical species for mediating zoonotic infectious disease spillover events. While there is a growing concern of increased antimicrobial resistance (AMR) globally during this pandemic, knowledge of AMR circulating between bats and humans is limited. In this paper, we have reviewed the evidence of AMR in bats and discussed the planetary health aspect of AMR to elucidate how this is associated with the emergence, spread, and persistence of AMR at the human-animal interface. The presence of clinically significant resistant bacteria in bats and wildlife has important implications for zoonotic pandemic surveillance, disease transmission, and treatment modalities. We searched MEDLINE through PubMed and Google Scholar to retrieve relevant studies (n = 38) that provided data on resistant bacteria in bats prior to 30 September 2022. There is substantial variability in the results from studies measuring the prevalence of AMR based on geographic location, bat types, and time. We found all major groups of Gram-positive and Gram-negative bacteria in bats, which are resistant to commonly used antibiotics. The most alarming issue is that recent studies have increasingly identified clinically significant multi-drug resistant bacteria such as Methicillin Resistant Staphylococcus aureus (MRSA), ESBL producing, and Colistin resistant Enterobacterales in samples from bats. This evidence of superbugs abundant in both humans and wild mammals, such as bats, could facilitate a greater understanding of which specific pathways of exposure should be targeted. We believe that these data will also facilitate future pandemic preparedness as well as global AMR containment during pandemic events and beyond.

'I Doubt Myself and Am Losing Everything I Have since COVID Came'-A Case Study of Mental Health and Coping Strategies among Undocumented Myanmar Migrant Workers in Thailand.

Migrant populations have always been vulnerable to a high burden of social exclusion, mental disorders, physical illnesses, and economic crises. The current COVID-19 pandemic has further created a frantic plight among them, particularly for undocumented migrant workers in the global south. We have conducted a mixed method study among the undocumented Myanmar migrant workers (UMMWs) in Thailand to explore how the COVID-19 disruption has impacted their mental health and what coping strategies they have adopted. Following the onset of COVID-19 and the recent coup d'état in Myanmar, our current study is the first attempt to understand the mental health status and predicament of this neglected migrant group. A total of 398 UMMWs were included in the online survey, of which 23 participated in qualitative interviews. The major mental health issues reported by the study participants were depression, generalized anxiety disorder, frustration, stress, and panic disorders, while loss of employment, worries about the pandemic, social stigma, lack of access to healthcare, lockdown, and fear of detention were the predominant contributing factors. In response, we identified two key coping mechanisms: coping at a personal level (listening to music, playing online game, praying, and self-motivation) and coping at a social level (chatting with family and friends and visiting religious institutions). These findings point to the importance of policy and intervention programs aimed at upholding mental health at such humanitarian conditions. Sustainable institutional mental health care support and social integration for the migrant workers, irrespective of their legal status, should be ensured.

Synthesis, in vitro bioassays, and computational study of heteroaryl nitazoxanide analogs.

Antiprotozoal drug nitazoxanide (NTZ) has shown diverse pharmacological properties and has appeared in several clinical trials. Herein we present the synthesis, characterization, in vitro biological investigation, and in silico study of four hetero aryl amide analogs of NTZ. Among the synthesized molecules, compound 2 and compound 4 exhibited promising antibacterial activity against Escherichia coli (E. coli), superior to that displayed by the parent drug nitazoxanide as revealed from the in vitro antibacterial assay. Compound 2 displayed zone of inhibition of 20 mm, twice as large as the parent drug NTZ (10 mm) in their least concentration (12.5 µg/ml). Compound 1 also showed antibacterial effect similar to that of nitazoxanide. The analogs were also tested for in vitro cytotoxic activity by employing cell counting kit-8 (CCK-8) assay technique in HeLa cell line, and compound 2 was identified as a potential anticancer agent having IC50 value of 172 µg which proves it to be more potent than nitazoxanide (IC50  = 428 µg). Furthermore, the compounds were subjected to molecular docking study against various bacterial and cancer signaling proteins. The in vitro test results corroborated with the in silico docking study as compound 2 and compound 4 had comparatively stronger binding affinity against the proteins and showed a higher docking score than nitazoxanide toward human mitogen-activated protein kinase (MAPK9) and fatty acid biosynthesis enzyme (FabH) of E. coli. Moreover, the docking study demonstrated dihydrofolate reductase (DHFR) and thymidylate synthase (TS) as probable new targets for nitazoxanide and its synthetic analogs. Overall, the study suggests that nitazoxanide and its analogs can be a potential lead compound in the drug development.

Targeting SARS-CoV-2 non-structural protein 13 via helicase-inhibitor-repurposing and non-structural protein 16 through pharmacophore-based screening.

Novel drug compound hunting was carried out for SARS-CoV-2 proteins with low mutation susceptibility. The probability of escape mutation and drug resistance is lower if conserved microbial proteins are targeted by therapeutic drugs. Mutation rate of all SARS-CoV-2 proteins were analyzed via multiple sequence alignment Non-Structural Protein 13 and Non-Structural Protein 16 were selected for the current study due to low mutation rate among viral strains and significant functionality. Cross-species mutation rate analysis for NSP13 and NSP16 showed these are well-conserved proteins among four coronaviral species. Viral helicase inhibitors, identified using literature-mining, were docked against NSP13. Pharmacophore-based screening of 11,375 natural compounds was conducted for NSP16. Stabilities of top compounds inside human body were confirmed via molecular dynamic simulation. ADME properties and LD50 values of the helicase inhibitors and Ambinter natural compounds were analyzed. Compounds against NSP13 showed binding affinities between -10 and -5.9 kcal/mol whereby ivermectin and scutellarein showed highest binding energies of -10 and -9.9 kcal/mol. Docking of 18 hit compounds against NSP16 yielded binding affinities between -8.9 and -4.1 kcal/mol. Hamamelitannin and deacyltunicamycin were the top compounds with binding affinities of -8.9 kcal/mol and -8.4 kcal/mol. The top compounds showed stable ligand-protein interactions in molecular dynamics simulation. The analyses revealed two hit compounds against each targeted protein displaying stable behavior, high binding affinity and molecular interactions. Conversion of these compounds into drugs after in vitro experimentation can become better treatment options to elevate COVID management.

Safety and efficacy of favipiravir for the management of COVID-19 patients: A preliminary randomized control trial.

Background: The novel coronavirus disease, commonly called COVID-19, has already killed millions of lives. Our study aimed to identify a safe and right drug for the management of such globally threatened COVID-19. Methods: This preliminary double-blinded randomized controlled trial was done among 57 hospitalized COVID-19 patients in the early stage of their illness. Of them, 29 patients received Favipiravir (FVP) and the remaining 28 patients received a placebo under the standard of care. Among the patients, 4 from Favipiravir (FVP) group and 3 from the placebo group were discontinued. The patients were observed regularly for a period of 10 days. Result: In our study, the FVP treated group showed accelerated viral clearance compared to the placebo-treated group. Assessment of chest X-ray showed remarkable improvement of pheumonia patient in group A compared to Group B. Hematological and Biochemical parameters such as total WBC count, neutrophil and lymphocyte counts were examined. No significant differences in the hematological parameters such as WBC count, neutrophil and lymphocyte counts in Group A and Group B patients. Liver transaminases levels were also stable in FVP treated group (average ALT ranges 39.4-46.2; AST 28.2-32.8). Conclusion: The drug Favipiravir displayed remarkable improvements in the clinical conditions and recovery of COVID-19 patients at the early stages of their infections.

Safety and Efficacy of Favipiravir for the management of COVID-19 Patients: A Randomized Control Trial

Background The novel coronavirus disease, commonly called COVID-19, has already killed millions of lives. Our study aimed to identify a safe and right drug for the management of such globally threatened COVID-19. Methods This preliminary double-blinded randomized controlled trial was done among 57 hospitalized COVID-19 patients in the early stage of their illness. Of them, 29 patients received Favipiravir (FVP) and the remaining 28 patients received a placebo under the standard of care. Among the patients, 4 from Favipiravir (FVP) group and 3 from the placebo group were discontinued. The patients were observed regularly for a period of 10 days. Result In our study, the FVP treated group showed accelerated viral clearance compared to the placebo-treated group. Assessment of chest X-ray showed remarkable improvement of pheumonia patient in group A compared to Group B. Hematological and Biochemical parameters such as total WBC count, neutrophil and lymphocyte counts were examined. No significant differences in the hematological parameters such as WBC count, neutrophil and lymphocyte counts in Group A and Group B patients. Liver transaminases levels were also stable in FVP treated group (average ALT ranges 39.4-46.2;AST 28.2-32.8). Conclusion The drug Favipiravir displayed remarkable improvements in the clinical conditions and recovery of COVID-19 patients at the early stages of their infections.

Evaluation of preventive, supportive and awareness building measures among international students in China in response to COVID-19: a structural equation modeling approach.

BACKGROUND: Education institutions promptly implemented a set of steps to prevent the spread of COVID-19 among international Chinese students, such as restrictive physical exercise, mask wear, daily health reporting, etc. Success of such behavioral change campaigns largely depends on awareness building, satisfaction and trust on the authorities. The purpose of this current study is to assess the preventive, supportive and awareness-building steps taken during the COVID-19 pandemic for international students in China, that will be useful for planning such a behavioral change campaign in the potential pandemic situation in other parts of the world. METHODS: We conducted an online-based e-questionnaire survey among 467 international students in China through WeChat. The data collection duration was from February 20, 2020 to March 10, 2020 and we focused on their level of awareness, satisfaction, and trust in authorities regarding pandemic measures. Simple bivariate statistics was used to describe the background characteristics of the respondents along with adoption of the partial least squares-structural equation modeling (PLS-SEM) as the final model to demonstrate the relationship between the variables. RESULTS: In our study, the leading group of the respondents were within 31 to 35 years' age group (39.82%), male (61.88%), living single (58.24%) and doctoral level students (39.8%). The preventive and supportive measures taken by students and/or provided by the respective institution or authorities were positively related to students' satisfaction and had an acceptable strength (ß = 0.611, t = 9.679, p < 0.001). The trust gained in authorities also showed an acceptable strength (ß = 0.381, t = 5.653, p < 0.001) with a positive direction. Again, the personnel awareness building related to both students' satisfaction (ß = 0.295, t = 2.719, p < 0.001) and trust gain (ß = 0.131, t = 1.986, p < 0.05) in authorities had a positive and acceptable intensity. Therefore, our study clearly demonstrates the great impact of preventive and supportive measures in the development of students' satisfaction (R2 = 0.507 indicating moderate relationship). The satisfied students possessed a strong influence which eventually helped in building sufficient trust on their institutions (R2 = 0.797 indicating above substantial relationship). CONCLUSIONS: The worldwide student group is one of the most affected and vulnerable communities in this situation. So, there is a profound ground of research on how different states or authorities handle such situation. In this study, we have depicted the types and magnitude of care taken by Chinese government and educational institutions towards international students to relieve the panic of pandemic situation. Further research and such initiatives should be taken in to consideration for future emerging conditions.